Development of the Fetal Brain Corticocortical Structural Network during the Second-to-Third Trimester Based on Diffusion MRI.

During the second-to-third trimester, the neuronal pathways of the fetal brain experience rapid development, resulting in the complex architecture of the interwired network at birth. While diffusion MRI-based tractography has been employed to study the prenatal development of structural connectivity network (SCN) in preterm neonatal and postmortem fetal brains, the in utero development of SCN in the normal fetal brain remains largely unknown. In this study, we utilized in utero dMRI data from human fetuses of both sexes between 26 and 38 gestational weeks to investigate the developmental trajectories of the fetal brain SCN, focusing on intrahemispheric connections. Our analysis revealed significant increases in global efficiency, mean local efficiency, and clustering coefficient, along with significant decrease in shortest path length, while small-worldness persisted during the studied period, revealing balanced network integration and segregation. Widespread short-ranged connectivity strengthened significantly. The nodal strength developed in a posterior-to-anterior and medial-to-lateral order, reflecting a spatiotemporal gradient in cortical network connectivity development. Moreover, we observed distinct lateralization patterns in the fetal brain SCN. Globally, there was a leftward lateralization in network efficiency, clustering coefficient, and small-worldness. The regional lateralization patterns in most language, motor, and visual-related areas were consistent with prior knowledge, except for Wernicke's area, indicating lateralized brain wiring is an innate property of the human brain starting from the fetal period. Our findings provided a comprehensive view of the development of the fetal brain SCN and its lateralization, as a normative template that may be used to characterize atypical development.

Fasudil attenuates oxidative stress-induced partial epithelial-mesenchymal transition of tubular epithelial cells in hyperuricemic nephropathy via activating Nrf2.

Anti-partial epithelial-mesenchymal transition (pEMT) treatment of renal tubular epithelial cells (TECs) represents a promising therapeutic approach. Hyperuricemia nephropathy (HN) arises as a consequence of hyperuricemia (HUA)-induced tubulointerstitial fibrosis (TIF). Studies have suggested that the Ras homolog member A (RhoA)/Rho-associated kinase (ROCK) pathway is a crucial signaling transduction system in renal fibrosis. Fasudil, a RhoA/ROCK inhibitor, has exhibited the potential to prevent fibrosis progress. However, its impact on the pEMT of TECs in HN remains unclear. Here, an HN rat model and an uric acid (UA)-stimulated human kidney 2 (HK2) cell model were established and treated with Fasudil to explore its effects. Furthermore, the underlying mechanism of action involved in the attenuation of pEMT in TECs by Fasudil during HN was probed by using multiple molecular approaches. The HN rat model exhibited significant renal dysfunction and histopathological damage, whereas in vitro and in vivo experiments further confirmed the pEMT status accompanied by RhoA/ROCK pathway activation and oxidative stress in tubular cells exposed to UA. Notably, Fasudil ameliorated these pathological changes, and this was consistent with the trend of ROCK silencing in vitro. Mechanistically, we identified the Neh2 domain of nuclear factor erythroid 2-related factor 2 (Nrf2) as a target of Fasudil for the first time. Fasudil targets Nrf2 activation and antagonizes oxidative stress to attenuate the pEMT of TECs in HN. Our findings suggest that Fasudil attenuates oxidative stress-induced pEMT of TECs in HN by targeting Nrf2 activation. Thus, Fasudil is a potential therapeutic agent for the treatment of HN.

Application of atmospheric cold plasma for zearalenone detoxification in cereals: Kinetics, mechanisms, and cytotoxicity analysis.

INTRODUCTION: Zearalenone (ZEN) is one of the most widely contaminated mycotoxins in world, posing a severe threat to human and animal health. Atmospheric cold plasma (ACP) holds great penitential in mycotoxin degradation. OBJECTIVES: This study aimed to investigate the degradation efficiency and mechanisms of ACP on ZEN as well as the cytotoxicity of ZEN degradation products by ACP. Additionally, this study also investigated the degradation efficiency of ACP on ZEN in cereals and its effect on cereal quality. METHODS: The degradation efficiency and products of ZEN by ACP was analyzed by HPLC and LC-MS/MS. The human normal liver cells and mice were employed to assess the cytotoxicity of ZEN degradation products. The ZEN artificially contaminated cereals were used to evaluate the feasibility of ACP detoxification in cereals. RESULTS: The results showed that the degradation rate of ZEN was 96.18 % after 30-W ACP treatment for 180 s. The degradation rate was dependent on the discharge power, and treatment time and distance. Four major ZEN degradation products were produced after ACP treatment due to the oxidative destruction of CC double bond, namely C18H22O7 (m/z = 351.19), C18H22O8 (m/z = 367.14), C18H22O6 (m/z = 335.14), and C17H20O6 (m/z = 321.19). L02 cell viability was increased from 52.4 % to 99.76 % with ACP treatment time ranging from 0 to 180 s. Mice results showed significant recovery of body weight and depth of colonic crypts as well as mitigation of glomerular and liver damage. Additionally, ACP removed up to 50.55 % and 58.07 % of ZEN from wheat and corn. CONCLUSIONS: This study demonstrates that ACP could efficiently degrade ZEN in cereals and its cytotoxicity was significantly reduced. Therefore, ACP is a promising effective method for ZEN detoxification in cereals to ensure human and animal health. Future study needs to develop large-scale ACP device with high degradation efficiency.

Causal Relationships Between Screen Use, Reading, and Brain Development in Early Adolescents.

The rise of new media has greatly changed the lifestyles, leading to increased time on these platforms and less time spent reading. This shift has particularly profound impacts on early adolescents, who are in a critical stage of brain development. Previous studies have found associations between screen use and mental health, but it remains unclear whether screen use is the direct cause of the outcomes. Here, the Adolescent Brain Cognitive Development (ABCD) dataset is utlized to examine the causal relationships between screen use and brain development. The results revealed adverse causal effects of screen use on language ability and specific behaviors in early adolescents, while reading has positive causal effects on their language ability and brain volume in the frontal and temporal regions. Interestingly, increased screen use is identified as a result, rather than a cause, of certain behaviors such as rule-breaking and aggressive behaviors. Furthermore, the analysis uncovered an indirect influence of screen use, mediated by changes in reading habits, on brain development. These findings provide new evidence for the causal influences of screen use on brain development and highlight the importance of monitoring media use and related habit change in children.

Reproducibility of Diffusion MRI-Based Tractography in the Fetal Brain.

BACKGROUND: Tractography based on diffusion MRI (dMRI) is a useful tool to study white matter of the developing brain. However, its application in fetal brains is limited due to motion artifacts and low resolution of in utero dMRI, leading to reduced reliability, which was scarcely investigated in previous studies. PURPOSE: To identify reliably traceable fibers in fetal brains and assess whether reproducibility varies with gestational age (GA) and varies between brain regions. STUDY TYPE: Prospective cohort study. SUBJECTS: A total of 44 healthy fetuses with GAs between 25 and 37 (31 ± 6). FIELD STRENGTH/SEQUENCE: 3-T, diffusion-weighted echo-planar imaging sequence (2-5 repeated dMRI scans within the same session per subject). ASSESSMENT: We fitted dMRI with constrained spherical deconvolution model and conducted tractography on eight fibers. We extracted volume, fractional anisotropy, and fiber count for each fiber and assessed the reproducibility of these metrics between repeated scans within each subject. Data were divided into two age-based subgroups (≤30 weeks, N = 28, and >30 weeks, N = 16) for further tests. STATISTICAL TESTS: The reproducibility were compared between fibers by analysis of variance and two-sample t tests. Multiple comparisons were corrected by the false discovery rate (5% was accepted). RESULTS: The reproducibility of the anterior thalamic radiation, inferior longitudinal fasciculus (ILF), genu of the corpus callosum (GCC), and body of the corpus callosum (BCC) significantly decreased with advancing GA (correlation coefficient = 0.525-0.823), as confirmed by group comparisons between fetuses in early GA (≤30 weeks) and late GA (>30 weeks) groups. Corticospinal tract, inferior fronto-occipital fasciculus, and GCC showed high reproducibility for fiber count (weighted dice average = 0.846 vs. 0.814), while BCC and ILF exhibited the lowest reproducibility in both age groups. DATA CONCLUSION: The study indicates that the reliability of fetal brain tractography depends on GA and varies among different fibers. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.